Abstract

Accumulation of amyloid peptide (Aβ) in senile plaques is a hallmark lesion of Alzheimer disease (AD). The design of molecules able to target the amyloid pathology in tissue is receiving increasing attention, both for diagnostic and for therapeutic purposes. Curcumin is a fluorescent molecule with high affinity for the Aβ peptide but its low solubility limits its clinical use. Curcumin-conjugated nanoliposomes, with curcumin exposed at the surface, were designed. They appeared to be monodisperse and stable. They were non-toxic in vitro, down-regulated the secretion of amyloid peptide and partially prevented Aβ-induced toxicity. They strongly labeled Aβ deposits in post-mortem brain tissue of AD patients and APPxPS1 mice. Injection in the hippocampus and in the neocortex of these mice showed that curcumin-conjugated nanoliposomes were able to specifically stain the Aβ deposits in vivo. Curcumin-conjugated nanoliposomes could find application in the diagnosis and targeted drug delivery in AD. From the Clinical EditorIn this preclinical study, curcumin-conjugated nanoliposomes were investigated as possible diagnostics and targeted drug delivery system in Alzheimer’s disease, demonstrating strong labeling of Aβ deposits both in human tissue and in mice, and in vitro downregulation of amyloid peptide secretion and prevention of Aβ-induced toxicity.

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